scholarly journals Homology Modeling and Optimized Expression of Truncated IK Protein, tIK, as an Anti-Inflammatory Peptide

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4358
Author(s):  
Yuyoung Song ◽  
Minseon Kim ◽  
Yongae Kim

Rheumatoid arthritis, caused by abnormalities in the autoimmune system, affects about 1% of the population. Rheumatoid arthritis does not yet have a proper treatment, and current treatment has various side effects. Therefore, there is a need for a therapeutic agent that can effectively treat rheumatoid arthritis without side effects. Recently, research on pharmaceutical drugs based on peptides has been actively conducted to reduce negative effects. Because peptide drugs are bio-friendly and bio-specific, they are characterized by no side effects. Truncated-IK (tIK) protein, a fragment of IK protein, has anti-inflammatory effects, including anti-rheumatoid arthritis activity. This study focused on the fact that tIK protein phosphorylates the interleukin 10 receptor. Through homology modeling with interleukin 10, short tIK epitopes were proposed to find the essential region of the sequence for anti-inflammatory activity. TH17 differentiation experiments were also performed with the proposed epitope. A peptide composed of 18 amino acids with an anti-inflammatory effect was named tIK-18mer. Additionally, a tIK 9-mer and a 14-mer were also found. The procedure for the experimental expression of the proposed tIK series (9-mer, 14-mer, and 18-mer) using bacterial strain is discussed.

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 397 ◽  
Author(s):  
Paolo Giuffrida ◽  
Sara Cococcia ◽  
Mariangela Delliponti ◽  
Marco Vincenzo Lenti ◽  
Antonio Di Sabatino

Inflammatory bowel disease (IBD) is caused by a dysregulated immune response against normal components of the intestinal microflora combined with defective functioning of anti-inflammatory pathways. Currently, all therapies approved for IBD manipulate the immune system by inhibiting pro-inflammatory mechanisms, such as tumor necrosis factor-α, gut-homing α4β7 integrin, interleukin-12/interleukin-23, and Janus kinases. However, some IBD patients are non-responders to these drugs, which are also associated with serious side effects. Thus, it has been hypothesized that therapies aimed at restoring anti-inflammatory signals, by exploiting the tolerogenic potential of cytokines (interleukin-10, transforming growth factor-β, granulocyte macrophage colony-stimulating factor), immune cells (regulatory T cells, tolerogenic dendritic cells), or mesenchymal stem cells, might offer promising results in terms of clinical efficacy with fewer side effects. In this review, we provide new insights into putative novel treatments aimed at restoring anti-inflammatory signaling pathways in IBD.


1980 ◽  
Vol 8 (5) ◽  
pp. 333-338 ◽  
Author(s):  
Alfred Becker ◽  
Rex T Hoffmeister

Fenbufen, a new butanoic acid derivative with anti-inflammatory properties, was evaluated in an open-label study. It was found that fenbufen was an effective anti-inflammatory agent with tolerable and acceptable potential side-effects. Its advantages appeared to be its long clinical half-life and relatively mild toxicity and/or allergic response.


2016 ◽  
Vol 27 (3) ◽  
pp. 244-254 ◽  
Author(s):  
Mathijs G.A. Broeren ◽  
Marieke de Vries ◽  
Miranda B. Bennink ◽  
Onno J. Arntz ◽  
Arjen B. Blom ◽  
...  

Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 501-505 ◽  
Author(s):  
Roldan Fernando ◽  
Richard Chan

With the advent of off-pump coronary bypass surgery, there is increasing demand for research in attenuating the deleterious effects of cardiopulmonary bypass (CPB). An improved understanding of the systemic inflammatory response syndrome (SIRS) has distinguished which areas of components have the most adverse effects and which are, in fact, anti-inflammatory. This classification of inflammatory components allows strategic treatment for those likely to cause the most clinically significant ‘effect’, suitably termed ‘effectors’. This article will identify current methods in treating ‘effectors’, as well as those components having anti-inflammatory effects. This article selectively features certain inflammatory components by: (1) grouping them as being ‘mediators’ or ‘effectors’; (2) relating them to interleukin-10 (IL-10) and treatments potentiating anti-inflammatory effects; (3) summarizing their mechanisms of action; (4) recognizing the time periods during bypass exhibiting peak levels; and (5) investigating current treatment methods and identifying their significance to ‘effectors’. A literature search in MEDLINE was performed, featuring articles of the English-language within the past 5 years. Because of the characteristic of having interlinked multi-component cascades, it is evident that treating SIRS with a one-dimensional method would be inadequate. This article not only confirms the importance of a multi-factorial therapeutic approach, but also targets the inflammatory components having the highest potential for causing direct tissue damage, known as ‘effectors’. In addition, previous studies have found IL-10 to have ‘regulatory effects’ during periods of excessive pro-inflammatory stimuli. These findings may arouse new ideas in exploring the area of anti-inflammatory cytokines. In fact, future treatments may suggest a new classification featuring ‘mediators’, ‘effectors’, and ‘regulators’.


1972 ◽  
Vol 1 (1) ◽  
pp. 18-21 ◽  
Author(s):  
T Hadidi ◽  
D K Asar ◽  
A Esmat

In a double-blind cross-over study the analgesic and anti-inflammatory action of ibuprofen 1600 mg/day in cases of rheumatoid arthritis has been compared with aspirin 4 g/day, metiazinic acid 1 .5 g/day and a placebo, lactose. Each compound was administered in identical capsules and in a totally randomised order to all patients studied. Assessment of the articular index, grip strength, knee score, erythrocyte sedimentation rate and subjective improvement was made before and after one week's treatment with each drug. In the doses used in this trial, the analgesic and anti-inflammatory activity of metiazinic acid in rheumatoid arthritis, was found to be approximately equipotent to that of aspirin, while ibuprofen seemed to be slightly more potent and to cause fewer side-effects.


1977 ◽  
Vol 5 (1) ◽  
pp. 18-25 ◽  
Author(s):  
F Chalem ◽  
P Farias ◽  
H Lizarazo ◽  
P Peña

A double-blind study was carried out to compare the effectiveness and tolerability of diftalone and phenylbutazone in thirty patients with classical or definite rheumatoid arthritis, randomly distributed between the two treatment groups. Both drugs were administered according to a progressively decreasing daily dosage schedule: 1,000 mg during the 1st week; 750 mg the 2nd week and 500 mg from the 3rd week on for diftalone; 400 mg, 300 mg, and 200 mg daily for the 1st, 2nd and from the 3rd week on respectively for phenylbutazone. The study lasted twelve weeks. The clinical controls and laboratory tests were performed weekly up to the 8th week, while the final evaluation was made at the end of the 3rd month. Twelve patients in the group receiving diftalone and fourteen in the phenylbutazone group completed the trial. Clinical improvement was observed in both groups. Effectiveness was somewhat more evident in the diftalone group. Tolerability was acceptable for both drugs, although the diftalone patients showed less frequent and intense side-effects than those treated with phyenylbutazone. No significant differences were found as regards the laboratory parameters, except a significant fall of the E.S.R. (p < 0·05) in the diftalone group. Diftalone seems to be an effective and safe anti-inflammatory agent in the treatment of rheumatoid arthritis.


1981 ◽  
Vol 9 (4) ◽  
pp. 253-256 ◽  
Author(s):  
G Kagan ◽  
L Huddlestone ◽  
P Wolstencroft

Forty patients in general practice with rheumatoid arthritis or osteoarthritis were identified as suffering from moderate pain and tenderness and moderate stiffness in excess of 30 minutes. After discontinuation of non-steroidal anti-inflammatory drugs for 2 weeks, a crossover study was conducted comparing the benefits of flufenamic acid, 100 mg, four times daily with placebo. At the same time, paracetamol at a dose up to 8 × 500 mg daily, could be used for pain which the patient judged to be unrelieved. Thirty-four patients completed the two 3-week test periods and twenty-one patients were improved in relation to morning stiffness and pain by flufenamic acid and twelve patients by placebo – a difference greater than would have occurred by chance (p = 0.05). At the same time, paracetamol consumption was reduced significantly from a mean of 91.29 tablets to 60.68 tablets for each 3-week period. Side-effects occurred in ten patients on placebo and fifteen patients on flufenamic acid. One patient on each medication had to discontinue for multiple side-effects. Diarrhoea occurred in two patients on flufenamic acid and in one patient on placebo. Flufenamic acid is clearly effective and side-effects do not occur more often than would be expected by chance when compared with placebo.


2013 ◽  
Vol 115 (6) ◽  
pp. 920-928 ◽  
Author(s):  
Maria L. Urso

Exercise, eccentric contractions, acute trauma, and disease are all causal mechanisms of skeletal muscle injury. After skeletal muscle is injured, it undergoes sequential phases of degeneration, inflammation, regeneration, and fibrosis. Events that occur in response to inflammation trigger regenerative processes. However, since inflammation causes pain, decreases skeletal muscle function, has a negative effect on performance, and contributes to fibrosis, which is one of the leading causes of delayed regeneration, the general practice has been to reduce inflammation. The problem with this approach is that preventing inflammation may hinder recovery. Current treatment options for inflammation are not necessarily effective and, in some cases, they may be unsafe. This review focuses on the question of whether the most beneficial course of treatment should be to block inflammation or if it is sensible to allow inflammatory processes to progress naturally. If blocking inflammation is perceived as a beneficial approach, it is not yet known at what time point during the inflammatory response it is most sensible to interfere. To address these issues, this review evaluates the effects of various anti-inflammatory agents on recovery processes in response to exercise-induced, traumatic, and disease-associated models of skeletal muscle injury. A collective analysis such as this should lay the foundation for future work that systematically manipulates the inflammatory response to most effectively promote regeneration and functional recovery in injured skeletal muscle, while reducing the negative effects of inflammatory processes such as pain and fibrosis.


BMJ ◽  
1967 ◽  
Vol 1 (5532) ◽  
pp. 69-75 ◽  
Author(s):  
P. Donnelly ◽  
K. Lloyd ◽  
H. Campbell

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